iPSC-derived astrocyte-neuron co-culture mitochondrial transfer in PD model

This study investigated whether iPSC-derived astrocytes can serve as mitochondrial donors to rescue injured dopaminergic neurons in an in vitro Parkinson's disease model. The researchers generated dopaminergic neurons and astrocytes from human iPSCs and hESCs, then established an astroglial-neuronal co-culture system. They used rotenone exposure to create neuronal injury mimicking PD pathology. The study examined intercellular mitochondrial transfer using Mito-Tracker Green labeling and tracked the transfer using immunocytochemistry and FACS analysis. Key findings included that healthy iPSC-derived astrocytes spontaneously release functional mitochondria into culture media, these mitochondria are internalized by injured neurons via a phospho-p38 dependent pathway, and the transferred mitochondria can significantly reverse dopaminergic neurodegeneration and axonal pruning caused by rotenone exposure. When astrocytic conditioned media was depleted of mitochondria by ultrafiltration, the neuroprotective effects were abolished, confirming that mitochondrial transfer was responsible for the rescue effect.